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We demonstrate that over-expression of miR-451 in human glioblastoma cell lines A172, LN229 and U251 significantly impacts cell proliferation, invasion and apoptosis. Our results suggest that these biologic effects may be due to modulated expression of a panel of proteins including Cyclin D1, p27, MMP 2/9 and Bcl-2. In addition, miR-451 regulates Akt expression in our studies. The transcription factor Akt1 plays a critical role in controlling a range of diverse cellular functions
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MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional and/or translational level by binding loosely complimentary sequences in the 3'untranslated regions (UTRs) of target mRNAs. Increased expression of several miRNAs, specifically hsa-miR-21, have been reported to modulate glioma development. Here we report downregulation of miR-451 in A172, LN229 and U251 human glioblastoma cells. Increased expression of miR-451 by administration of miR-451 mimics oligonucleotides reversed the biology of each of the three cell lines, inhibiting cell growth, inducing G0/G1 phase arrest and increasing cell apoptosis. Further, treatment with miR-451 mimics oligonucleotides diminished the invasive capacity of these cells, as the number of cells invading through matrigel was significantly decreased. Akt1, CyclinD1, MMP-2, MMP-9 and Bcl-2 protein expression decreased, and p27 expression increased in a dose-dependent manner with miR-451 mimics oligonucleotides. Taken together, these studies reveal miR-451 impacts glioblastoma cell proliferation, invasion and apoptosis, perhaps via regulation of the PI3K/AKT signaling pathway. We propose an essential role for miR-451 as a tumor-suppressor of human glioma.